It is thought that Leukotriene B4 (5-[S], 12-[R]-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid; it is abbreviated to LTB4 hereafter.) is a lipid mediator producted by arachidonate cascade and that promotes the migration of leukocytes, the production of active oxygen and the release of lysosomal enzyme, etc., by binding to receptor in the presence of membrane surface, and that plays a key role for organism such as the inflammatory reaction and the defense to bacterial infection etc.
Two kinds of BLT1 and BLT2, which are G-protein coupled receptors, have been already reported as LTB4 receptor (J. Exp. Med., Volume 192, Number 3, 2000, 421-). It has been confirmed that these receptors, which bind to G-protein such as Gi and Gq, etc., cause the induction of intracellular signal such as the rise of intracellular calcium concentration and the suppression of adenylate cyclase activity, etc., by binding of the ligand LTB4. Affinity of LTB4 to both receptors is different though the homology in amino acid sequence between BLT1 and BLT2 is high (45%) and BLT1 specifically strongly binds to LTB4 with Kd value 0.15 nM, BLT2 weakly binds to LTB4 with Kd value 22 nM. It is reported that BLT1 is strongly expressed on leukocyte and is very strictly and organ-specifically expressed, while BLT2 is most strongly expressed in spleen and lymphocyte and sincerely expressed in a lot of organs including liver and ovary.
Thus, because both receptors are different the reactiveness to LTB4 and the expression distribution, it is guessed that both receptors would play a mutually different role in vivo. Therefore, it is thought that a compound that acts on BLT1 shows a pharmacological action different from a compound that acts on BLT2. So far, it has been thought that the compound that acts on BLT1 is useful for diseases including bronchial asthma and articular rheumatism to which leukocytic infiltration relates. On the other hand, it has been thought that the compound that acts on BLT2 is useful for prevention and/or therapy of BLT2 mediated diseases, e.g., human immunodeficiency virus (hereafter, it is abbreviated to HIV) infection, rejection to transplant, transplant rejection, graft-versus-host disease, autoimmune disease (e.g., systemic lupus erythematous, articular rheumatism, myasthenia gravis and sclerosis multiple, etc.), allergic disease (e.g., atopic dermatitis and bronchial asthma, etc.), inflammation, infectious disease, ulcus, lymphoma, carcinoma, leukosis, arteriosclerotic, hepatitis, liver cirrhosis or cancer, etc. However, there is no report that BLT2 is highly expressed in small intestine and skin keratinocyte and that the compound that binds to BLT2 is useful for prevention and/or therapy of intestinal disease including ulcerative colitis or skin disease including psoriasis and dermatitis so far.
And, there is no report about an agonist or antagonist specific to BLT2 and usage thereof at all so for.
On the other hand, it is known that a compound containing biphenyl structure has an antagonism against angiotensin II and a regulatory action on peroxisome proliferator-activated receptor (e.g., see patent literature 1, 2, 3 and 4).    Patent document 1: JP-A-06-72985    Patent document 2: JP-A-06-184086    Patent document 3: JP-A-06-211814    Patent document 4: WO99/12534